Winter Peter S, Wood Kris C
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA; Program in Genetics and Genomics, Duke University, Durham, NC, USA; Current address: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Trends Cancer. 2018 May;4(5):333-335. doi: 10.1016/j.trecan.2018.02.004. Epub 2018 Mar 7.
Oncogenic KRAS can activate numerous effector pathways to drive malignant progression. However, the relationships between specific effectors and oncogenic phenotypes, and the extent to which these relationships vary across heterogeneous tumors, are incompletely understood. Recently in Cell Reports, a team of scientists described an innovative, combinatorial siRNA-based approach to functionally link KRAS effectors and phenotypes in a large panel of cancer cell lines. Central to this work was the identification of two major subtypes of KRAS-mutant cancers with distinct effector landscapes and tractable therapeutic vulnerabilities.
致癌性KRAS可激活众多效应通路以驱动恶性进展。然而，特定效应分子与致癌表型之间的关系，以及这些关系在异质性肿瘤中的变化程度，目前尚未完全明确。最近，在《细胞报告》杂志上，一组科学家描述了一种创新的、基于组合式小干扰RNA（siRNA）的方法，用于在大量癌细胞系中从功能上关联KRAS效应分子与表型。这项工作的核心是鉴定出KRAS突变型癌症的两种主要亚型，它们具有不同的效应分子格局和易于处理的治疗弱点。
